Objective: Establish at the subcellular level the nature of the defect of the megakaryocytes and platelets in the myeloproliferative disorders (MPD). Approach and Progress: Our preliminary studies demonstrated striking ultrastructural abnormalities of the platelets and the presence of small, dystrophic circulating megakaryocytes in MPD. As the next step, we have conducted a combined functional-anatomical electron microscopic study using conventional in vitro aggregometry in conjunction with EM. So far we have studied a group of patients with refractory anemia and myelomonocytic leukemia. We have found defective aggregation coupled with abnormalities of the platelet aggregates as seen with EM (manuscripts in preparation) and a distinct platelet granulopathy (results published or in press). Finally, we have described abnormalities of the bone marrow megakaryocytes in preleukemia and myelomonocytic leukemia. Future studies will be directed toward subcellular fractionation of the platelets and biochemical analysis.